# US 7,744,902 B2 · Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes

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- Number: US 7,744,902 B2
- Document ID: US7744902B2
- Status: Granted
- Kind: B2
- Application number: 11/033,055
- Filed: 2005-01-10
- Published: 2006-02-02
- Granted: 2010-06-29
- Earliest claimed: 1999-07-09
- Assignees: The United States of America as represented by the Department of Health and Human Services
- Inventors: Christine D. Krempl; Peter L. Collins; Brian R. Murphy; Ursula Buchholz; Stephen S. Whitehead
- Web page: https://patentgrep.com/patent/US7744902B2

## CPC

- C07K 14/005: from viruses
- C07H 21/02: with ribosyl as saccharide radical
- C12N 7/00: Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00)
- C12N 15/86: Viral vectors
- A61K 39/00: Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53)
- A61K 2039/5254: {avirulent or attenuated}
- A61K 2039/5256: {expressing foreign proteins}
- A61K 2039/543: {intranasal}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2319/00: Fusion polypeptide
- C12N 2760/18522: New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
- C12N 2760/18543: viral genome or elements thereof as genetic vector
- C12N 2760/18561: Methods of inactivation or attenuation
- C12N 2760/18562: by genetic engineering
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Recombinant respiratory syncytial virus (RSV) having the position of genes shifted within the genome or antigenome of the recombinant virus are infectious and attenuated in humans and other mammals. Gene shifted RSV are constructed by insertion, deletion or rearrangement of genes or genome segments within the recombinant genome or antigenome and are useful in vaccine formulations for eliciting an anti-RSV immune response. Also provided are isolated polynucleotide molecules and vectors incorporating a recombinant RSV genome or antigenome wherein a gene or gene segment is shifted to a more promoter-proximal or promoter-distal position within the genome or antigenome compared to a wild type position of the gene in the RSV gene map. Shifting the position of genes in this manner provides for a selected increase or decrease in expression of the gene, depending on the nature and degree of the positional shift. In one embodiment, RSV glycoproteins are upregulated by shifting one or more glycoprotein-encoding genes to a more promoter-proximal position. Genes of interest for manipulation to create gene position-shifted RSV include any of the NS1, NS2, N, P, M, SH, M2(ORF1), M2(ORF2), L, F or G genes or a genome segment that may be part of a gene or extragenic. A variety of additional mutations and nucleotide modifications are provided within the gene position-shifted RSV of the invention to yield desired phenotypic and structural effects.

## Claims

### Claim 1

An isolated infectious RSV, which is rBRSV/A2-NS1+2, deposited with the American Type Tissue Culture Collection as accession number PTA-10444.

### Claim 2

An isolated infectious RSV, which is rBRSV/A2-NS1+2GF, deposited with the American Type Tissue Culture Collection as accession number PTA-10445.

### Claim 3

An isolated infectious RSV, which is rBRSV/A2-MSHGF, deposited with the American Type Tissue Culture Collection as accession number PTA-10446.

### Claim 4

An isolated polynucleotide molecule comprising a recombinant RSV genome or antigenome encoding rBRSV/A2-NS1+2, rBRSV/A2-NS1+2GF, or rBRSV/A2-MSHGF.